The invention relates to novel inhibitors of human tryptase which are used in the pharmaceutical industry for the production of medicaments.
Human tryptase is a serine proteinase which is the predominant protein present in human mast cells. The term tryptase covers four closely related enzymes (xcex1, I, II/xcex2, III; possessing 90 to 98% sequence identity) (cf. Miller et al., J. Clin. Invest. 84 (1989) 1188-1195; Miller et al., J. Clin. Invest. 86 (1990) 864-870; Vanderslice et al., Proc. Natl. Acad. Sci., USA 87 (1990) 3811-3815). With the exception of xcex1-tryptase (Schwartz et al., J. Clin. Invest. 96 (1995) 2702-2710; Sakai et al., J. Clin. Invest. 97 (1996) 988-995), the enzymes are activated intracellularly and stored in catalytically active form in secretory granules.
As compared with other known serine proteinases, such as trypsin or chymotrypsin, tryptase exhibits some exceptional properties (Schwartz et al., Methods Enzymol. 244, (1994), 88-100; G. H. Caughey, xe2x80x9cMast cell proteases in immunology and biology.xe2x80x9d Marcel Dekker, Inc., New York, 1995). Tryptase obtained from human tissue has a noncovalently linked tetrameric structure which has to be stabilized by heparin or other proteoglycans in order to be proteolytically active.
Low-molecular-weight compounds are described as tryptase inhibitors in the international applications WO 95/32945, WO 96/09297 and WO 98/04537.
It has now been found that the compounds of the formula I described in more detail below possess surprising and particularly advantageous properties.
The invention relates to compounds of the formula I 
in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are hydrogen, 1-4C-alkyl, 1-4C-alkyl which is wholly or partially substituted by fluorine, or hydroxyl, or R1 and R2 together, and including the carbon atom to which they are bonded, are xe2x80x94C(O)xe2x80x94 or a 5- or 6-membered, optionally substituted cyclic hydrocarbon,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94 or xe2x80x94S(O)2xe2x80x94,
T is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
R5 and R6 are identical or different and are hydrogen or 1-4C-alkyl,
R7 is hydrogen, 1-4C-alkyl, phenyl or pyridyl,
R8 is 1-4C-alkoxy, N(R81)R82, piperidino or morpholino,
R81 and R82 are identical or different and are hydrogen or 1-4C-alkyl,
R9 is hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
n is 0, 1, 2 or 3,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are a 4-11C-heteroaryl or 2-7C-heterocycloalkyl radical which contains at least one ring nitrogen,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
1-4C-Alkyl represents straight-chain or branched alkyl radicals having from 1 to 4 carbon atoms. The butyl, the iso-butyl, the sec-butyl, the tert-butyl, the propyl, the isopropyl, the ethyl and the methyl radical may be mentioned by way of example.
Examples of 1-4C-alkyl which is entirely or partially substituted by fluorine which may be mentioned are the 2,2,3,3,3-pentafluoropropyl, the perfluoroethyl, the 1,2,2-trifluoroethyl, the 1,1,2,2-tetrafluoroethyl, the 2,2,2-trifluoroethyl, the trifluoromethyl and the difluoromethyl radicals.
Examples of a 5- or 6-membered cyclic hydrocarbon which may be mentioned are cyclopentane or cyclohexane.
1-4C-Alkoxy represents radicals which, in addition to the oxygen atom, contain a straight-chain or branched alkyl radical having from 1 to 4 carbon atoms. The butoxy, the iso-butoxy, the sec-butoxy, the tert-butoxy, the propoxy, the isopropoxy and, preferably, the ethoxy and the methoxy radical may be mentioned by way of example.
1-4C-Alkylene represents straight-chain or branched 1-4C-alkylene radicals, for example the methylene [xe2x80x94CH2xe2x80x94], the ethylene [xe2x80x94CH2xe2x80x94CH2xe2x80x94], the trimethylene [xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94], the tetramethylene [xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94], the 1,2-dimethylethylene [xe2x80x94CH(CH3)xe2x80x94CH(CH3)xe2x80x94], the 1,1-dimethylethylene [xe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94], the 2,2-dimethylethylene [xe2x80x94CH2xe2x80x94C(CH3)2xe2x80x94], the isopropylidene [xe2x80x94C(CH3)2xe2x80x94] or the 1-methylethylene [xe2x80x94CH(CH3)xe2x80x94CH2xe2x80x94] radical.
1-3C-Alkylene represents straight-chain or branched 1-3C-alkylene radicals, for example the methylene [xe2x80x94CH2xe2x80x94], the ethylene [xe2x80x94CH2xe2x80x94CH2xe2x80x94], the trimethylene [xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94], the isopropylidene [xe2x80x94C(CH3)2xe2x80x94] or the 1-methylethylene [xe2x80x94CH(CH3)xe2x80x94CH2xe2x80x94] radical.
If m has the meaning 0, the group xe2x80x94(C(O))mxe2x80x94 is then a bond.
If p has the meaning 0, the group xe2x80x94(C(O))pxe2x80x94 is then a bond.
If n has the meaning 0, the group xe2x80x94(CH2)nxe2x80x94 is then a bond.
4-11C-Heteroaryl is an optionally substituted monocyclic or bicyclic aromatic hydrocarbon which contains from 4 to 11 C atoms and at least one ring nitrogen atom; in addition, one or more of the carbon atoms can be replaced by ring heteroatoms selected from the group O, N or S. In bicycles, at least one of the rings is aromatic. Pyrid-4-yl, pyrid-3-yl, pyrimidin-5-yl, imidazol-1-yl and benzimidazol-5-yl may be mentioned by way of example.
2-7C-Heterocycloalkyl is an optionally substituted monocyclic saturated or partially saturated hydrocarbon which contains from 2 to 7 C atoms and at least one ring nitrogen atom; in addition, one or more carbon atoms can be replaced by ring heteroatoms selected from the group O, N or S. Piperid-4-yl, piperazin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl and morpholin-2-yl may be mentioned by way of example.
5-12C-Arylene is an optionally substituted divalent monocyclic or bicyclic aromatic hydrocarbon radical which possesses from 5 to 12 C atoms, with at least one of the rings being aromatic in the case of the bicyclic aromatic hydrocarbon radicals. The free valencies can both be located on the aromatic ring or on the nonaromatic ring, or one can be located on the aromatic ring and one on the nonaromatic ring. 1,4-Phenylene, 1,3-phenylene, 1,4-naphthylene and 2,6-naphthylene may be mentioned by way of example.
5-12C-Heteroarylene is an arylene radical, as previously defined, in which from 1 to 4 C atoms are replaced by heteroatoms selected from the group O, N and S. 2,5-Furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,5-benzofuranylene, 2,6-quinolinylene and 4,2-thiazolylene may be mentioned by way of example.
3-8C-Cycloalkylene is an, optionally substituted, divalent monocyclic saturated or partially saturated hydrocarbon radical which possesses from 3 to 8 C atoms. The 1,3-cyclopentylene, the 1,3-cyclohexylene and, preferably, the 1,4-cyclohexylene radical may be mentioned by way of example.
3-8C-Heterocycloalkylene is a cycloalkylene radical, as previously defined, in which from 1 to 3 C atoms are replaced by heteroatoms selected from the group O, N and S. The 1,4-piperidinylene, the 1,4-piperazinylene, the 2,5-pyrrolidinylene, the 4,2-imidazolidinylene and, preferably, the 4,1-piperidinylene radical may be mentioned by way of example.
1-4C-Alkoxycarbonyl is a carbonyl group to which one of the abovementioned 1-4C-alkoxy radicals is bonded. The methoxycarbonyl (CH3Oxe2x80x94C(O)xe2x80x94) and the ethoxycarbonyl (CH3CH2Oxe2x80x94C(O)xe2x80x94) radical may be mentioned by way of example.
1-4C-Alkylcarbonyloxy is a carbonyloxy group to which one of the abovementioned 1-4C-alkyl radicals is bonded. The acetoxy radical (CH3C(O)xe2x80x94Oxe2x80x94) may be mentioned by way of example.
Several of the groups listed under M possess, either in themselves or due to their substitution, one or more chiral centers. The invention therefore encompasses both all the pure enantiomers and all the pure diastereomers and also their mixtures in any mixing ratio.
The groups Z1 and Z2, respectively, are located, by definition, between the groups B9 and B11 (-B9-Z1-B11-) and B10 and B12 (-B10-Z2-B12-), respectively. Correspondingly, in the divalent groups (e.g. 2,6-indolylene) which are mentioned by way of example, the first number is that of the site for linkage to the B9 or B10 group, respectively, and the second number is that of the site for linkage to the B11 or B12 group, respectively.
In the context of this application, the expression xe2x80x9cterminal nitrogen atomxe2x80x9d in each case refers to a nitrogen atom in the groups denoted X1, X2, Y1 and Y2.
If the groups X1 and/or X2 contain only one nitrogen atom, this nitrogen atom is the terminal nitrogen atom.
If the groups X1 and/or X2 contain a plurality of nitrogen atoms, the nitrogen atom which is located furthest from the atom via which the bond to groups B9 (B11) or B10 (B12) is effected is the terminal nitrogen atom.
If the groups Y1 and/or Y2 contain only one ring nitrogen atom, this ring nitrogen atom is the terminal nitrogen atom.
If the groups Y1 and/or Y2 contain a plurality of ring nitrogen atoms, the ring nitrogen atom which is located furthest from the atom via which the bond with the groups B9 or B10 is effected is the terminal nitrogen atom.
According to the invention, the direct route between the nitrogen atoms which act as terminal nitrogen atoms in the groups defined as X1 (Y1) or X2 (Y2) is the number of bonds which is obtained by counting the bonds which represent the shortest possible link between the terminal nitrogen atoms.
The following example is used to illustrate how the number of bonds on the direct route between two terminal nitrogen atoms is determined: 
Here, the direct route encompasses 26 bonds.
The inhibitors according to the invention are bifunctional inhibitors, i.e. inhibitors having two reactive functional groups. These groups are such that they can bind specifically to active sites of tryptase. The two functional groups of the inhibitor preferably bind to active sites in different monomer subunits of the tryptase tetramer.
The inhibitors according to the invention are suitable for inhibiting human tryptase. Human tryptase is understood as meaning, in particular, the human enzyme xcex2-tryptase with the EC No. 3.4.21.59.
Depending on substitution, all acid addition salts or all salts with bases are suitable salts for compounds of the formula I. Those which may in particular be mentioned are the pharmacologically tolerated salts of the inorganic and organic acids which are customarily used in pharmacy. Suitable salts of this nature are, on the one hand, water-soluble and water-insoluble acid addition salts with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, with the acids being employed, when preparing the salt, in an equimolar quantity ratio or in a quantity ratio which differs from this depending on whether the acid is a monobasic or polybasic acid and on which salt is desired.
On the other hand, salts with bases are also suitable. Examples of salts with bases which may be mentioned are alkali (lithium, sodium or potassium) or calcium, aluminum, magnesium, titanium, ammonium, meglumin or guanidinium salts, with the bases also in this case being employed, when preparing the salt, in an equimolar quantity ratio, or in a quantity ratio which differs from this.
Salts which are not pharmacologically tolerated and which can, for example, initially arise as process products when producing the compounds according to the invention on an industrial scale, are converted into pharmacologically tolerated salts using methods known to the skilled person.
The skilled person knows that the compounds according to the invention, and also their salts, when they are isolated in crystalline form, for example, can contain varying quantities of solvents. The invention therefore also encompasses all solvates and, in particular, all hydrates of the compounds of the formula I, as well as all solvates and, in particular, all hydrates of the salts of the compounds of the formula I.
One embodiment (embodiment a) of the compounds according to the invention of the formula I is that in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94 xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are hydrogen, 1-4C-alkyl, 1-4C-alkyl which is wholly or partially substituted by fluorine, or hydroxyl, or R1 and R2 together, and including the carbon atom to which they are bonded, are xe2x80x94C(O)xe2x80x94 or a 5- or 6-membered, optionally substituted cyclic hydrocarbon,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94 or xe2x80x94S(O)2xe2x80x94,
R8 is 1-4C-alkoxy, N(81)R82, piperidino or morpholino,
R81 and R82 are identical or different and are hydrogen or 1-4C-alkyl,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are a 4-11C-heteroaryl or 2-7C-heterocycloalkyl radical which contains at least one ring nitrogen,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
Compounds of embodiment a which are to be emphasized are those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are hydrogen, 1-4C-alkyl, 1-4C-alkyl which is wholly or partially substituted by fluorine, or hydroxyl, or R1 and R2 together, and including the carbon atom to which they are bonded, are xe2x80x94C(O)xe2x80x94 or a 5- or 6-membered, optionally substituted cyclic hydrocarbon,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94 or xe2x80x94S(O)2xe2x80x94,
R8 is 1-4C-alkoxy, N(R81)R82, piperidino or morpholino,
R81 and R82 are identical or different and are hydrogen or 1-4C-alkyl,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or straight-chain or branched 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, 5-methylimidazol-4-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, benzimidazol-4-yl or benzimidazol-5-yl,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naphthylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3, 6-indazolylene, 2, 6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or carbonyl groups.
Compounds of embodiment a which are in particular to be emphasized are those in which
A1 and A2 are identical or different and are xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94NHxe2x80x94C(O)xe2x80x94,
A3 and A4 are identical or different and are xe2x80x94C(O)-NHxe2x80x94 or are selected from the group 
where W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond,
M is selected from one of the following groups 
K1 is -B7-(C(O))m-B9-X1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or xe2x80x94CH2xe2x80x94 (methylene),
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-2C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are amino, amidino or guanidino,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-cyclohexylene or 1,4-piperazinylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or two carbonyl groups.
Preferred compounds of embodiment a are those in which
A1 and A2 are identical or different and are xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94NHxe2x80x94C(O)xe2x80x94,
A3 and A4 are identical or different and are xe2x80x94C(O)-NHxe2x80x94 or are selected from the group 
where W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond,
M is selected from one of the following groups 
K1 is -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or xe2x80x94CH2xe2x80x94 (methylene),
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or xe2x80x94CH2xe2x80x94 (methylene),
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are amino, amidino or guanidino,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-cyclohexylene or 1,4-piperazinylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or two carbonyl groups.
Particularly preferred compounds of embodiment a are bis{4-[4-(4-aminomethylcyclohexanoyl)piperazin-1-yl]-carbonyl}-4,4xe2x80x2-diaminodiphenyl ether, bis{4-[(3-aminomethyl)benzoylpiperazin-1-yl]carbonyl}-4,4xe2x80x2-diaminodiphenyl ether, di{4-[4-(4-aminomethyl)cyclohexanoyl-amino]piperidin-1-ylcarbamoyl}cyclohexylmethane, 2,2-bis[4-(4-guanidinylbenzylamino)carbonylmethoxyphenyl]-propane, 2,2-bis[4-(10-amino-3,6-diaza-2,5-dioxodecyloxyphenyl] propane and 2,2-bis{4-[4-(4-aminomethylbenzylcarbamoyl)-1-piperazinylcarbonyloxy]phenyl}propane, and also the salts of these compounds.
Another embodiment (embodiment b) of the compounds according to the invention of the formula I is that in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94O- or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are hydrogen, 1-4C-alkyl, 1-4C-alkyl which is wholly or partially substituted by fluorine, or hydroxyl, or R1 and R2 together, and including the carbon atom to which they are bonded, are xe2x80x94C(O)xe2x80x94 or a 5- or 6-membered, optionally substituted cyclic hydrocarbon,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94 or xe2x80x94S(O)2xe2x80x94,
T is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
R5 and R6 are identical or different and are hydrogen or 1-4C-alkyl,
R7 is hydrogen, 1-4C-alkyl, phenyl or pyridyl,
R9 is hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
n is 0, 1, 2 or 3,
K1 is -B7-(C(O)) B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are a 4-11C-heteroaryl or 2-7C-heterocycloalkyl radical which contains at least one ring nitrogen,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
Compounds of embodiment b which are to be emphasized are, on the one hand, those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O).xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are 1-4C-alkyl which is wholly or partially substituted by fluorine, or R1 and R2 together, and including the carbon atom to which they are bonded, are a 5- or 6-membered, optionally substituted cyclic hydrocarbon,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94S(O)2xe2x80x94,
T is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
R5 and R6 are identical or different and are hydrogen or 1-4C-alkyl,
R7 is pyridyl,
K1 is -B7-(C(O)) -B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are a 4-11C-heteroaryl or 2-7C-heterocycloalkyl radical which contains at least one ring nitrogen,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
On the other hand, compounds of embodiment b which are to be emphasized are those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are 1-4C-alkyl or together, and including the carbon atom to which they are bonded, are carbonyl,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94Sxe2x80x94 (sulfur),
T is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
R5 and R6 are identical or different and are hydrogen or 1-4C-alkyl,
R7 is hydrogen, 1-4C-alkyl or phenyl,
K1 is -B7-(C(O) )m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
Compounds of embodiment b which are furthermore to be emphasized are those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur)xe2x80x94, xe2x80x94S(O)2xe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
R9 is hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
n is 0, 1, 2 or 3,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7- (C (O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl
Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thioncarbonyl group.
Compounds of embodiment b which are in particular to be emphasized are, on the one hand, those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are 1-4C-alkyl which is wholly or partially substituted by fluorine, or R1 and R2 together, and including the carbon atom to which they are bonded, are a 5- or 6-membered, optionally substituted cyclic hydrocarbon,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94S(O)2xe2x80x94,
T is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
R5 and R6 are identical or different and are hydrogen or 1-4C-alkyl,
R7 is pyridyl,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, 5-methylimidazol-4-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, benzimidazol-4-yl or benzimidazol-5-yl,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naphthylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or two carbonyl groups.
Compounds of embodiment b which are in particular to be emphasized are, on the other hand, compounds of the formula I in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R1 and R2 are identical or different and are 1-4C-alkyl or together, and including the carbon atom to which they are bonded, are carbonyl,
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
E is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
G is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94Sxe2x80x94 (sulfur),
T is xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94 or a bond,
R5 and R6 are identical or different and are hydrogen or 1-4C-alkyl,
R7 is hydrogen, 1-4C-alkyl or phenyl,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9 Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl, Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naphthylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or two carbonyl groups.
Compounds of embodiment b which are in particular to be emphasized are furthermore those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
R3 and R4 are identical or different and are hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
R9 is hydrogen or one, two or three identical or different 1-4C-alkyl radicals,
n is 0, 1, 2 or 3,
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naphthylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or two carbonyl groups.
Compounds of embodiment b which are in particular to be emphasized are, in addition, pyridine-2,6-dicarbobis[4-(3-aminomethylbenzoyl)-1-piperazide], pyridine-2,6-dicarbobis[4-(trans-4-aminomethylcyclohexanoyl)-1-piperazide], 2,6-dimethyl-4-phenylpyridine-3,5-dicarbobis[4-(3-aminomethylbenzoyl)-1-piperazide], pyridine-2,6-dicarbobis[4-(3-aminomethylbenzoylamino)-1-piperidide] and pyridine-2,6-dicarbobis[4-(4-aminomethylcyclohexylcarbonylamino)-1-piperidide], and also the salts of these compounds.
A further embodiment (embodiment c) of the compounds of the formula I is that in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1 B11 X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are a 4-4C-heteroaryl or 2-7C-heterocycloalkyl radical which contains at least one ring nitrogen,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
Compounds of embodiment c which are to be emphasized are those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur), xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94S(O)2xe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
U is xe2x80x94Oxe2x80x94 (oxygen) or xe2x80x94CH2xe2x80x94 (methylene),
V is xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94Sxe2x80x94 (sulfur) or xe2x80x94CH2xe2x80x94 (methylene), and
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
where
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or l-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl,
Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene,
with each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocycloalkyl additionally, for its part, being able to be substituted by one, two or three substituents selected from the group hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms, two carbonyl groups or one carbonyl group and one thiocarbonyl group.
Compounds of embodiment c which are in particular to be emphasized are those in which
A1 and A2 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94 (oxygen), xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
A3 and A4 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94 or a bond, or are selected from the group 
where
W is the group xe2x80x94C(O)xe2x80x94 or a bond,
A5 and A6 are identical or different and are xe2x80x94C(O)xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or a bond,
M is selected from one of the following groups 
K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7- (C ))m-B9-Z1-B11-X1,
K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2,
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene,
B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene,
m is 0 or 1,
p is 0 or 1,
X1 and X2 are identical or different and are selected from the following groups 
where
R10 is 1-4C-alkyl,
Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl,
Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naphthylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene,
and in which 24 to 40 bonds must be present on the direct route between the terminal nitrogen atoms,
the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes which contain a nitrogen atom, and their salts,
with all those compounds being excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond, with this thereby resulting in the direct linkage of two heteroatoms or two carbonyl groups.
The compounds of the formula I are composed of a large number of divalent building blocks (M, A1, A2, A3, A4, A5, A6, B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, Z1 and Z2). In principle, they can be synthesized starting from any one of these building blocks. In the case of compounds of the formula I which are constructed to a large extent symmetrically, preference is given to starting the synthesis with the central building block M; by contrast, it can be advantageous to synthesize compounds of the formula I which are predominantly asymmetrical starting with one of the end groups K1 or K2.
In this connection, the building blocks are always linked together in accordance with the same pattern, which is known per se to the skilled person.
The skilled person knows that the compounds of the formula I can be synthesized building block by building block; alternatively, relatively large fragments, consisting of several individual building blocks, can first of all be constructed, with these fragments then being assembled into the whole molecule.
Amino [xe2x80x94NHxe2x80x94], ether [xe2x80x94Oxe2x80x94], thioether [xe2x80x94Sxe2x80x94], keto [xe2x80x94C(O)xe2x80x94], thioketo [xe2x80x94C(S)xe2x80x94], sulfonyl [xe2x80x94S(O)2xe2x80x94], ester [xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94], amide [xe2x80x94C(O)xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94C(O)xe2x80x94], sulfonamide [xe2x80x94SO2xe2x80x94NHxe2x80x94, xe2x80x94NHxe2x80x94SO2xe2x80x94], carbamate [xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94NHxe2x80x94], carbamide (xe2x80x94NHxe2x80x94C(O)xe2x80x94NHxe2x80x94) or carbonate [xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94] bridges occur in the compounds of the formula I as a result of the meanings which the individual building blocks of the compounds of the formula I can assume.
The manner in which such bridges are prepared is known per se to the skilled person, and suitable methods, and starting compounds for preparing them, are described, for example, in March, Advanced Organic Chemistry, Reactions, Mechanisms and Structure, Third Edition, 1985, John Wiley and Sons.
For example, ether and thioether bridges can be prepared by the method of Williamson.
Keto or thioketo bridges can, for example, be introduced as components of larger building blocks, such as 1,3-dichloroacetone.
Sulfonyl bridges can be obtained, for example, by oxidizing thioether bridges.
A large number of methods are known for synthesizing ester bridges. Mention may be made here, by way of example, of the reaction of acids with alcohols, preferably using H2SO4 or p-toluenesulfonic acid as catalyst; or with the addition of a water-extracting agent, such as a molecular sieve or a carbodiimide. The reaction of acid chlorides with alcohols may also be mentioned at this point.
There is also a large number of known methods for preparing amide bridges. The reaction of acid chlorides with primary or secondary amines may be mentioned here as an example. In addition, reference may also be made to all the methods which have been developed for peptide chemistry. Correspondingly, sulfonamide bridges can be synthesized from sulfonyl chlorides and primary or secondary amines.
Carbamate bridges can be prepared, for example, by reacting chlorocarbonic esters with amines. The chlorocarbonic esters can, for their part, be synthesized from alcohols and phosgene.
The addition of alcohols to isocyanates constitutes another variant for synthesizing carbamate bridges.
In a similar way to carbamate bridges, carbonate bridges can be prepared from chlorocarbonic esters by reacting them with alcohols (instead of amines).
Carbamide bridges can be prepared, for example, by reacting isocyanates with amines.
It is also possible to convert compounds of the formula I by derivatization into other compounds of the formula I. Thus, for example, compounds of the formula I which have a nitrogen-containing heteroaryl or heterocycloalkyl building block can be converted by oxidation into the corresponding N-oxides.
The N oxidation is effected in a manner with which the skilled person is also familiar, for example using hydrogen peroxide in methanol or m-chloroperoxybenzoic acid in dichloromethane at room temperature. The skilled person is familiar, on the basis of his specialist knowledge, with the detailed reaction conditions which are required for carrying out the method.
It is furthermore known to a person skilled in the art that, if a starting material or intermediate contains a plurality of reactive centers, it may be required to protect one or more reactive centers temporarily by protective groups so that a reaction can take place selectively at the desired reaction center. A detailed description of how a large number of proven protective groups are used is given, for example, in T. W. Greene, Protective Groups in Organic Synthesis, John Wiley and Sons, 1991.
The substances according to the invention are isolated and purified in a manner known per se, for example by the solvent being distilled off in vacuo and the resulting residue being recrystallized from a suitable solvent or being subjected to one of the customary purification methods such as column chromatography on a suitable support material.
Salts are obtained by dissolving the free compound in a suitable solvent, for example in a chlorinated hydrocarbon, such as methylene chloride or chloroform, or a low molecular weight aliphatic alcohol (ethanol, isopropanol), which contains the desired acid or base, or to which the desired acid or base is subsequently added. The salts are isolated by filtering, reprecipitation or precipitation with a substance which does not dissolve the addition salt, or by evaporating off the solvent. Resulting salts can be converted, by alkalizing or acidifying, into the free compounds, which can be converted into salts once again. In this way, salts which are not tolerated pharmacologically can be converted into salts which are tolerated pharmacologically.
The preparation of compounds of the formula I may be demonstrated, by way of example, with the aid of the following Examples 1 to 12 and FIGS. 1 to 12. Other compounds of the formula I can be prepared analogously or using the methods which are cited above and which are known per se to the skilled person.
FIGS. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 show formula schemes for preparing bifunctional inhibitors according to the invention.